2004, volume 20, issue 4


Therapeutic drug monitoring of valproic ac id in patients with psychiatric disturbances

Halina Matsumoto, Elżbieta Woźny, Anna Dziklińska, Małgorzata Abramowska, Szymon Niemcewicz, Waldemar Szelenberger
Farmakoterapia w Psychiatrii i Neurologii, 2004, 4, 423-433

In the pharmacotherapy of psychiatric disturbances valproic acid (valproate) is very often applied in combination with other psychotropic drugs. The purpose of this study was to assess the level of valproic acid (VPA) in serum of the patients subjected to the monitoring of the drug concentration. 130 patients, in 2 years of the observation, have been examined. All patients were treated with VPA in combination with neuroleptics (I or II generation) or antidepressants. The range of VPA concentration, determined by FPIA method did not show significant differences in the studied groups of patients. Among all results obtained, 39% indicated VPA concentration on a subtherapeutic range with the mean value: 34,4 ± 11,2 µg/ml, 58% were within the limits of the therapeutic range (50-100 µg/ml) with mean value: 66,7 ± 11,3 µg/ml and 3% on a potentially toxic range (mean: 107,9 ± 6,6 µg/ml).The authors conclude that therapeutic monitoring of VPA concentration is useful in the patients submitted to polypharmacotherapy, and they indicate that it is necessary to limit polypragmasy, because of its influence upon the efficacy and safety of the treatment.


Obesity and metabolic abnormalities in schizophrenic patients, drug naive and during antipsychotic drug administration

Małgorzata Rzewuska
Farmakoterapia w Psychiatrii i Neurologii, 2004, 4, 435-463

In a cohort of drug-naive subjects with schizophrenia untreated with medications, visceral fat content was threefold higher than in age- and BMI – matched control subjects. Drug-naive patients presenting with their first episode had an increased prevalence of impaired fasting glucose, were more insulin resistant, and had higher plasma levels of glucose, insulin and cortisol than did matched control subjects.
Case reports, case series, observational analytic epidemiologic studies, and randomized trials raise the possibility, that some antipsychotic drugs likely due to drugs - induced weight gain and hasten associated metabolic abnormalities including hyperglycemia, diabetes mellitus, and dyslipidemia. Most of phenotiazines and second generation antipsychotics (SGAs) can cause a rapid increase in body weight in the first few months of therapy that may not reach a plateau after l year of treatment. Use of many SGAs has been associated with the new onset, or exacerbation of diabetes. Several of these events occurred within a few weeks of initiating drugs treatment. In some, but not all eases, hyperglicemia promptly resolved after the medication was discontinued. Several repoits documented recurrent hyperglicemia after another challenge with the same drug. The data consistently show an increased risk for diabetes in patients treated with clozapine or olanzapine compared with patients not receiving treatment, with classical neuroleptics, or with other SGAs. The risk in patients taking risperidone and quetiapine is less clear. Aripiprazole and ziprazidone have relatively limited epidemiological data, but available clinical trial experience with these drugs has not shown an increased risk for diabetes. Patients treated with olanzapine and clozapine have higher fasting and postprandial insulin levels, than patients treated with FGAs, even after adjusting for body weight.
This both drugs produce the greatest weight gain, are associated with the greatest increases in total cholesterol, LDL cholesterol and triglycerides and with dereased HDL cholesterol. When prescribing an SGA, a commitment to baseline screening and follow-up monitoring is essential in order to mitigate the like hood of developing cardio-vascular disease, diabetes or other diabetes complications.
The assessment for initiation of any antipsychotic can determine, if the patients is overweight (BMI 25-29,9), has pre-diabetes (fasting plasma glucose 100-125 mg/dL) or diabetes (FPG ≥ 126 mg/dL), hypertension (blood pressure > 140/90 mmHg), or dyslipidemia. If any of these conditions are identified, appropriate treatment should be initiated.
The standards of pharmacotherapy in patients with metabolic syndrome are presented.


Comparing the efficacy of olanzapine (Zolafren, ADAMED) and perazine in hospitalized patients with schizophrenia: results of a multicenter, randomized, 8-week clinical trial

Bartosz Łoza, Marek Masiak, Mariusz Bartyzel, Paulina Chałupka, Bartłomiej Krzewiński, Jolanta Masiak, Anna Mosiołek, Mariusz Perucki, Artur De Rosier, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2004, 4, 465-476

objectives: This paper reports on the results of randomized multicenter study comparing, the efficacy and tolerability of olanzapine (Zolafren, ADAMED) and perazine in acute schizophrenic episode.
Methods: The study included 86 schizophrenic patients, hospitalized because of the exacerbation of the illness. Forty-four patients received olanzapine, 10-20 mg/day (mean 18.4 mg/day), and 42 patients received perazine, 100-600 mg/day (mean 294 mg/day), for 8 weeks. The groups of patients did not differ as to demographic and clinical parameters and the initial intensity of symptoms.
Results: In both groups of patients, a statistically significant clinical improvement was observed. The improvement was bigger in the group receiving olanzapine, as measured in Positive and Negative Syndrome Scale (total score, positive symptoms, negative symptoms, general psychopathology) Clinical Global Impression and Calgary Depression Rating Scale. Treatment with olanzapine compared with perazine was associated with significantly lower risk of side-effects, including extrapyramidal symptoms, as well as with significantly lower risk of withdrawal from the study. Both drugs did not cause significant changes in laboratory parameters and electrocardiographic examinations except for higher cholesterol level in the perazine group. Olanzapine caused a moderate weight gain (mean 2.8 kg).
Conclusions: The results of the study suggest that olanzapine (Zolafren, ADAMED) when used in the treatment of acute schizophrenic episode shows good efficacy and tolerability. Compared with perazine, treatment with olanzapine is associated with better clinical improvement and less side-effects.


The effect of donepezil on cognitive junctions in patients with Alzheimer s disease previously treated with rivastigmine

Alina Borkowska, Monika Wiłkość, Marta Tomaszewska, Wiktor Dróżdż, Janusz Rybakowski
Farmakoterapia w Psychiatrii i Neurologii, 2004, 4, 477-483

The aim of this study was to assess the effect of donepezil on cognitive functions in patients with Alzheimer’s disease (AD) previously treated with rivastigmine. Thirty-one AD patients, 11 males and 20 females, aged 56-86 (mean 71 years), with duration of illness 2-4 (mean 3 years) and duration of rivastigmine treatment 3-12 (mean 8 months) participated in the study. Compared with the results obtained before donepezil administration, a significant improvement in Mini Mental State Examination score (after 3 and 6 months), Alzheimer Disease Assessment Scale (ADAS-cog) and Trail making Test (TMT) A after 3,6 and 12 months of treatment was found. No improvement was observed on TMT B, measuring the efficiency of visuo-spatial working memory and in both parts of Stroop test, measuring the efficiency of verbal working memory. The results obtained suggest a positive effect of donepezil on global cognitive functioning in patients with AD previously treated with rivastigmine who had insufficient improvement or did not tolerate the drug. Donepezil may also slow down the progression of deterioration of cognitive functions connected with frontal lobe activity in AD patients.


Trazodone in the treatment of BPSD

Iwona Makowska, Radosław Magierski, Iwona Kłoszewska
Farmakoterapia w Psychiatrii i Neurologii, 2004, 4, 485-494

Psychiatric symptoms and behavioral disturbances are common in patients with dementia. Agitated or aggressive behaviors occur in approximately 30% to 60% of patients with dementia and are a major source of mortality, particularly in nursing homes. Such behaviors often reflect patient distress and can contribute to physical injury, caregiver distress, need for institutionalization, and healthcare costs. Preventing and treating agitated behavior in patients with dementia are critical clinical goals. However, the choice of medication in clinical practice continues to be directed largely by local pharmacotherapy culture rather than empirical treatment guidelines. We’re still looking for an effective and safe drug. One of the investigated drugs is trazodone. Several studies have reported its anti-agitation efficacy. It has been associated with improvements in agitation, aggression, irritability, anxiety, affective disturbance and sleep problems among patients with dementia and was also well tolerated.